Human major histocompatibility system (MHS) serologically identifiable antigens serve as important genetic markers for immune response (Ir) and disease susceptibility genes, genetic mapping of chromosome #6, and studies of cell interactions. The primary objective of this proposal is to identify new serologically detectable human lymphocyte alloantigens and to characterize inter-relationships among MHS antigens. Sera from parous female blood donors will be screened by cytotoxicity against panels of peripheral blood lymphocytes (PBL's) and B lymphocytes from selected unrelated individuals and from menbers of well-studied families. Lysostrip and F(ab')2 blocking techniques will be used to confirm nonidentity with previously defined antibodies. Murine xenogeneic monoclonal antibodies against PBL's or B lymphocytes will be analyzed to identify antibodies to MHS and non-MHS human lymphocyte alloantigens. Inter-relationships among different HLA antigens will be studied based upon the hypotheses that some crossreactivity, antigen splits, and CYNAP reactions result from different spatial orientation, related to a Bw4/Bw6 backbone, of particular HLA antigens and their bound antibodies. Antibody binding to cells and activation of components of complement by CYNAP antibodies will be assayed.